DESCRIPTION: We will build implantable, fiberoptic, zinc sensors for neurology and neuroscience. These sensors will utilize proprietary, genetically engineered proteins (on optical fibers) to provide real-time monitoring of intracranial Zn2+. The sensors are needed both for basic research on zinc-containing neurons and in the emergency room/ICU for monitoring acutely brain-injured patients. Monitoring intracranial Zn2+ is clinically important because the Zn2+/- ion is a contributing cause of excitotoxic neuron injury. In head trauma, ischemia, and seizures, merely chelating extracellular zinc substantially reduces the number of neurons showing degenerative changes after the insult. Our clinical zinc sensor is designed to be inserted through a ventriculostomy, beside the traditional intracranial pressure probe. In acutely brain-injured patients, rising levels of Zn2+ would alert surgical, ER or ICU staff to intervene aggressively with zinc-release blockers, zinc chelators, zinc channel blockers, or other therapies against zinc-mediated neurotoxicity. For the basic neuroscience laboratory, our fiberoptic sensors will allow the real-time monitoring of the synaptic release of zinc into the extracellular milieu. Just as older methods for monitoring transmitter release (voltametry, microdialysis) revolutionized our understanding of classical transmitters, so too can optical monitoring of Zn2+ release inform our understanding of zinc-modulated synaptic function. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE